The effects of sleep disturbances on patients receiving methadone treatment for opioid use disorder: cortical thickness evidence

Background Sleep disturbances are prevalent among patients with methadone maintenance treatment (MMT) for opioid use disorder (OUD), yet the neurobiological implications remain poorly understood. So we investigated cortical thickness between the MMT and the MMT with sleep disturbances (MMTS) patients to determine the interplay between MMT, sleep disturbances, and cortical remodeling. Methods This study was approved by the ethics committee of the Affiliated Suzhou Hospital, Medical School of Nanjing University (IRB2024070). We recruited 30 MMT and 33 MMTS participants in this study. All subjects underwent a high-resolution MRI for calculating the cortical thickness by the surface-based morphometry (SBM). Meanwhile, sleep quality of all subjects were recorded using the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI), and evaluated the relationship between the cortical alternations and sleep disturbances. Results There were significant increases of cortical thickness in MMTS patients within the left entorhinal cortex, right pericalcarine cortex, and left frontalpole cortex compared to the MMT patients after adjusting for covariates (all p 0.05). The increase thickness of the left frontalpole cortex was positively correlated with the PSQI ( p = 0.038, r=0.27) and its sub-items (Sleep Quality, p = 0.04, r=0.27; Daytime Dysfunction, p = 0.037, r=0.28). While the increase thickness of the left entorhinal cortex (Sleep Quality, p = 0.017, r=0.31; Sleep Duration, p = 0.041, r=0.27) and right pericalcarine coetex(Sleep Latency, p = 0.036, r=0.27) showed associations with specific sleep items. No correlations emerged with the ISI. Conclusions These findings identify increased cortical thickness in the left entorhinal, right pericalcarine, and left frontalpole cortices in MMTS patients, potentially driven by the receptor effects of methadone, neuroinflammation, or synaptic plasticity linked to sleep disturbances. The study underscored sleep disturbances as a critical modifier of neuroanatomical alternations in MMT, advocating for sleep-targeted interventions to mitigate relapse risk and optimize MMT strategies. Longitudinal studies integrating objective sleep measures were warranted to validate these biomarkers for clinical prognostication.